The Peoples Republic of China has the second highest overall case burden of TB in the world (behind India). The WHO Global Tuberculosis Report 2014 estimated that, in 2013, China had 1,300,000 cases of TB, with a prevalence of 94/100,000 population and an incidence of 70/100,000 population. For MDR TB, China has the 2nd highest annual number of cases in the world. Among all new TB cases in 2013, an estimated 5.7% (45,000 people) were MDR-TB. Among retreated TB cases in 2013, an estimated 26% (9,200 people) were MDR. Henan Province is Chinas third largest province by population, with about 94 million people. By global population rankings, that would make it the 13th largest country in the world. About ten percent of all new pulmonary TB cases in China each year occur in Henan Province and reported MDR TB rates in Henan are among the highest across the country. In partnership with provincial health authorities in Zhengzhou, the capital of Henan Province, the Tuberculosis Research Section is developing the sites capacity to conduct high-quality clinical research. In 2009, NIAID Deputy Director Hugh Auchincloss signed an Implementing Arrangement with the Henan Provincial Bureau of Health to establish a collaborative research center. Our first study, a prospective, longitudinal natural history study entitled A Natural History Study of Tuberculosis in China: Correlates of a Successful Response in Treatment (NIAID 10-I-N060), began enrollment in 2010 with all subjects completing the study in 2014. Data analyses are ongoing, including interferon-gamma release assay responses in TB subjects on treatment and quantitative changes on CT scans of patients on treatment over time. An automated CT reading algorithm is being developed which can quantitate the amount of diseased lung by lung segment and compare changes over time in a very reproducible manner. In another analysis, one patient from this cohort was noted to have dramatically increased sputum AFB bacillary load 6 weeks after starting treatment, after which bacterial counts slowly decreased. This patient had multiple anatomically discrete sites of pulmonary disease that responded different to treatment, suggesting that heterogeneous Mtb populations existed. Deep whole genome sequencing of serial sputum isolates confirmed three dominant subclones at week 6, two of which were not observed at baseline. The three subclones had different drug resistance patterns, which may explain the heterogeneous response to treatment. This result suggests that branched evolution of Mtb in vivo can lead to divergent Mtb subclones and heterogeneous responses to treatment within a single individual. In FY2014, a new study initiated at this site, titled Feasibility and accuracy of a novel Xpert XDR cartridge for rapid molecular detection of drug resistant Mycobacterium tuberculosis in sputum (DMID Protocol Number 13-0029; DMID Funding Mechanism: Award Number N01AI90500C). This study is being conducted in conjunction with Susan Dorman at Johns Hopkins University under a grant from DMID. The primary objective of this prospective, cross-sectional study is to estimate the sensitivity and specificity of the investigational Xpert XDR cartridge for detection of M. tuberculosis resistance to isoniazid, fluoroquinolones, and aminoglycosides. With the first generation Xpert MTB/RIF cartridge only able to detect rifampin resistance, this second generation cartridge would provide a significant advancement in rapidly determining multidrug and extensively drug resistant tuberculosis. The study was conducted in Zhengzhou, Henan Province and Seoul, South Korea. The study began enrollment on June 5, 2014 and, as of June 15, 2015, the study completed with 240 subjects enrolled at the China site. Data analyses are ongoing with preliminary analyses showing that the sensitivity/specificity of the new Xpert XDR cartridge is 99.7%/87.5% compared to the Xpert MTB/RIF cartridge. Resistance test results are still being analyzed and, in early analyses, appear to have good correlation with MGIT phenotypic resistance testing results.